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Leukotriene B4 receptor BLT1 mediates early effector T cell recruitment

Nature Immunology volume 4, pages 982–990 (2003)Cite this article

Abstract

Leukotriene B4 (LTB4) was originally described as a potent lipid myeloid cell chemoattractant, rapidly generated from innate immune cells, that activates leukocytes through the G protein–coupled receptor BLT1. We report here that BLT1 is expressed on effector CD4+ T cells generated in vitro as well as in vivo when effector T cells migrate out of the lymphoid compartment and are recruited into peripheral tissues. BLT1 mediated LTB4-induced T helper type 1 (TH1) and TH2 cell chemotaxis and firm adhesion to endothelial cells under flow, as well as early CD4+ and CD8+ T cell recruitment into the airway in an asthma model. Our findings show that the LTB4-BLT1 pathway is involved in linking early immune system activation and early effector T cell recruitment.

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Figure 1: BLT1 expression in effector CD4+ cells differentiated in vitro.
Figure 2: Chemotactic responses of wild-type and BLT1-deficient naive, TH1 and TH2 CD4+ cells to LTB4 and CXCL12.
Figure 3: Conversion of TH1 and TH2 CD4+ cell rolling to firm arrest by LTB4 and CXCL12.
Figure 4: BLT1 expression in CD4+ effector cells generated in vivo, and trafficking of these effectors in a primary immune response.
Figure 5: Trafficking of wild-type and BLT1-deficient T cells in an active immunization asthma model.
Figure 6: Trafficking of wild-type and BLT1-deficient T cells in an adoptive transfer asthma model.
Figure 7: OVA-specific IgE and IgG titers.

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Acknowledgements

The authors thank C.P. Leary for technical assistance. This work is funded by National Institutes of Health grants K08-HL04087 (A.M.T.), F32-AI54107 (S.K.B.), F32-AI50399 (B.D.M.), R01-HL65584 (R.E.G.), and R01-AI050892, R01-AI46999, R01-AI40618, R01-CA69212 and PPG-DK5005 (A.D.L.), and by a Warren-Whitman-Richardson Fellowship (Harvard Medical School; S.A.I.).

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  1. Andrew M Tager and Shannon K Bromley: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Rheumatology, Center for Immunology and Inflammatory Diseases, Allergy and Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, 02114, Massachusetts, USA

    Andrew M Tager, Shannon K Bromley, Benjamin D Medoff, Sabina A Islam, Scott D Bercury, Erik B Friedrich, Andrew D Carafone, Robert E Gerszten & Andrew D Luster

  2. Pulmonary and Critical Care Unit, Massachusetts General Hospital, Harvard Medical School, Boston, 02114, Massachusetts, USA

    Andrew M Tager & Benjamin D Medoff

  3. Cardiology Division, Massachusetts General Hospital, Harvard Medical School, Boston, 02114, Massachusetts, USA

    Robert E Gerszten

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Tager, A., Bromley, S., Medoff, B. et al. Leukotriene B4 receptor BLT1 mediates early effector T cell recruitment. Nat Immunol 4, 982–990 (2003). https://doi.org/10.1038/ni970

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